| http://purl.uniprot.org/citations/34635651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34635651 | http://www.w3.org/2000/01/rdf-schema#comment | "Abnormal activation of epidermal growth factor receptor (EGFR) drives non-small cell lung cancer (NSCLC) development. EGFR mutations-mediated resistance to tyrosine-kinase inhibitors (TKIs) is a major hurdle for NSCLC treatment. Here, we show that F-box protein FBXL2 targets EGFR and EGFR TKI-resistant mutants for proteasome-mediated degradation, resulting in suppression of EGFR-driven NSCLC growth. Reduced FBXL2 expression is associated with poor clinical outcomes of NSCLC patients. Furthermore, we show that glucose-regulated protein 94 (Grp94) protects EGFR from degradation via blockage of FBXL2 binding to EGFR. Moreover, we have identified nebivolol, a clinically used small molecule inhibitor, that can upregulate FBXL2 expression to inhibit EGFR-driven NSCLC growth. Nebivolol in combination with osimertinib or Grp94-inhibitor-1 exhibits strong inhibitory effects on osimertinib-resistant NSCLC. Together, this study demonstrates that the FBXL2-Grp94-EGFR axis plays a critical role in NSCLC development and suggests that targeting FBXL2-Grp94 to destabilize EGFR may represent a putative therapeutic strategy for TKI-resistant NSCLC."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-021-26222-x"xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Chen H."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Cao Y."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Ding L."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Guo R."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Gao Y."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "He Y."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Hu Q."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Fu M."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Li F."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Li L."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Luo Y."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Li R."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Niu M."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Dong B."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Qi S."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Yang J."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Yu S."xsd:string |
| http://purl.uniprot.org/citations/34635651 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |